Rheumatoid arthritis (RA) is an arthritic disease of unknown cause(s). Although numerous attempts have been made to identify an etiologic agent(s) for RA, none has to date been identified. It has been shown in earlier studies conducted by our group at the University of Tennessee and at other institutions that there is detectable autoimmunity to type II collagen in many patients with RA. A recently published limited phase II study suggested that soluble type II chick-collagen given orally to patients with RA [after discontinuation of disease modifying anti- rheumatic drugs (DMARDs)] was associated with clinical improvement of the disease, perhaps by inducing tolerance to type II collagen. The majority of patients with RA are eventually treated with DMARDs, and many continue to exhibit disease activity while on "maximal DMARD regimens". Since in clinical practice it may be useful to add oral type II collagen to such DMARD regimens, it is important to determine whether orally administered soluble type II collagen as an "add on" or "adjunctive" therapy will benefit such patients. Therefore, this supplemental application wishes to test the hypothesis that orally administered soluble bovine type II collagen will decrease clinical signs and symptoms of rheumatoid arthritis (RA) and laboratory parameters characteristic of RA activity in patients whose disease is active while on DMARD and/or NSAID therapy. This hypothesis will be tested by the following specific aims: 1) Determine whether orally administered soluble bovine type II collagen improves clinical signs and symptoms of RA patients on or off DMARD and/or NSAID therapy. 2) Determine whether laboratory parameters of disease activity positively correlate with clinical response. 3) Determine whether a particular HLA-DR haplotype correlates with a positive or negative response to type II collagen treatment. It is anticipated that this study will provide evidence for or against the efficacy of bovine type II collagen as a treatment for routine chronic patients with active RA on or off DMARDs.